Are advanced oxidation protein products potential uremic toxins?

Abstract

Oxidative stress, defined as a disruption of the equilibrium between the generation of oxidants and the activity of anti-oxidant systems, plays a significant role in the development of the inflammatory syndrome associated with chronic renal failure and hemodialysis. In our recent work, the aim of which was to better characterize oxidative stress in dialysis patients, we described the presence of oxidized protein products, which we have termed advanced oxidation protein products (AOPP), in the plasma of dialysis patients and we proposed AOPP as new markers of oxidative stress and potential inflammatory mediators. AOPP represent an exquisite marker of phagocyte-derived oxidative stress, and their role in the pathophysiology of chronic renal failure and dialysis-related complications might be of great importance. Regarding the mechanisms of generation of AOPP, we pointed out the importance of myeloperoxidase and the subsequent generation of chlorinated oxidants, previously considered solely as microbicidal agents, in the formation of AOPP. Indeed, AOPP appear to act as true inflammatory mediators since they are able to trigger the oxidative burst and the synthesis of inflammatory cytokines in neutrophils, as well as in monocytes. Thus, it could be hypothesized that the AOPP, which arise from the reaction between chlorinated oxidants and plasma proteins, constitute new uremic toxins with pro-inflammatory effects.